crossing96/oncoscreening huggingface dataset:
Norcantharidin triggers cell death and DNA damage through S-phase arrest and ROS-modulated apoptotic pathways in TSGH 8301 human urinary bladder carcinoma cells.	Norcantharidin (NCTD) is one of the ingredients of blister beetles which have been used in Chinese medicine for a long time. The purpose of this study was to investigate the inhibitory effects of NCTD on TSGH 8301 human bladder cancer cells in vitro and the mechanisms through which it exerts its anticancer action. Cell morphological analysis was performed using a phase-contrast microscope. The percentage of viable cells, cell cycle distribution, sub-G1 phase (apoptosis), reactive oxygen species (ROS) production and the levels of mitochondrial membrane potential (∆Ψ(m)) were analyzed by flow cytometry. DNA condensation and damage were determined by DAPI staining and comet assay. Apoptosis-associated protein level changes in TSGH 8301 cells following exposure to NCTD were examined, measured and determined by western blotting. Analysis of protein translocation was conducted by immunostaining and confocal laser microscopy. The results indicated that NCTD promoted cytotoxic effects, including the induction of cell morphological changes and the decrease in the percentage of viability, the induction of S-phase arrest as well as sub-G1 phase (apoptosis) in TSGH 8301 cells. The activities of caspase-3 and -9 were upregulated following NCTD treatment. Western blotting indicated that NCTD upregulated Fas, FasL, Bax, Bid, cytochrome c, caspase-3, -8 and -9 that led to the induction of apoptosis through the Fas extrinsic pathway. Furthermore, NCTD induced AIF and Endo G that were released from mitochondria to induce apoptosis through the mitochondrial-independent pathway. NCTD upregulated ROS production, downregulated ∆Ψ(m) and ERK, JNK, p38 protein kinases in TSGH 8301 cells. These findings suggest that NCTD triggers apoptosis in TSGH 8301 human bladder cancer cells via the Fas receptor, activation of the caspse-8, -9 and -3, mitochondrial-dependent and -independent pathways. NCTD may be useful for developing new therapeutic regimens for the treatment of bladder cancer.	bladder
Chemotherapy and radiotherapy improve bladder cancer outcomes.	Chemoradiotherapy decreases recurrence risk in muscle-invasive bladder cancer.	bladder
p16 expression is not associated with human papillomavirus in urinary bladder squamous cell carcinoma.	Squamous cell carcinoma of the urinary bladder is unusual and of unknown etiology. There is a well-established association between human papillomavirus (HPV) infection and the development of cervical and head/neck squamous cell carcinomas. However, the role of HPV in the pathogenesis of squamous cell carcinoma of the urinary bladder is uncertain. The purposes of this study were to investigate the possible role of HPV in the development of squamous cell carcinoma of the urinary bladder and to determine if p16 expression could serve as a surrogate marker for HPV in this malignancy. In all, 42 cases of squamous cell carcinoma of the urinary bladder and 27 cases of urothelial carcinoma with squamous differentiation were investigated. HPV infection was analyzed by both in situ hybridization at the DNA level and immunohistochemistry at the protein level. p16 protein expression was analyzed by immunohistochemistry. HPV DNA and protein were not detected in 42 cases of squamous cell carcinoma (0%, 0/42) or 27 cases of urothelial carcinoma with squamous differentiation (0%, 0/15). p16 expression was detected in 13 cases (31%, 13/42) of squamous cell carcinoma and 9 cases (33%, 9/27) of urothelial carcinoma with squamous differentiation. There was no correlation between p16 expression and the presence of HPV infection in squamous cell carcinoma of the bladder or urothelial carcinoma with squamous differentiation. Our data suggest that HPV does not play a role in the development of squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation. p16 expression should not be used as a surrogate marker for evidence of HVP infection in either squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation as neither HVP DNA nor protein is detectable in these neoplasms.	bladder
Molecular diagnostic trends in urological cancer: biomarkers for non-invasive diagnosis.	The early detection of urological cancers is pivotal for successful patient treatment and management. The development of molecular assays that can diagnose disease accurately, or that can augment current methods of evaluation, would be a significant advance. Ideally, such molecular assays would be applicable to non-invasively obtained body fluids, enabling not only diagnosis of at risk patients, but also asymptomatic screening, monitoring disease recurrence and response to treatment. The advent of advanced proteomics and genomics technologies and associated bioinformatics development is bringing these goals into focus. In this article we will discuss the promise of biomarkers in urinalysis for the detection and clinical evaluation of the major urological cancers, including bladder, kidney and prostate. The development of urine-based tests to detect urological cancers would be of tremendous benefit to both patients and the healthcare system.	bladder
A systematic review of neoadjuvant and adjuvant chemotherapy for muscle-invasive bladder cancer.	CONTEXT: Muscle-invasive bladder cancer (MIBC) is a disease with a pattern of predominantly distant and early recurrences. Neoadjuvant cisplatin-based combination chemotherapy has demonstrated improved outcomes for MIBC. OBJECTIVE: To review the data supporting perioperative chemotherapy and emerging regimens for MIBC. EVIDENCE ACQUISITION: Medline databases were searched for original articles published before April 1, 2012, with the search terms bladder cancer, urothelial cancer, radical cystectomy, neoadjuvant chemotherapy, and adjuvant chemotherapy. Proceedings from the last 5 yr of major conferences were also searched. Novel and promising drugs that have reached clinical trial evaluation were included. EVIDENCE SYNTHESIS: The major findings are addressed in an evidence-based fashion. Prospective trials and important preclinical data were analyzed. CONCLUSIONS: Cisplatin-based neoadjuvant combination chemotherapy is an established standard, improving overall survival in MIBC. Pathologic complete response appears to be an intermediate surrogate for survival, but this finding requires further validation. Definitive data to support adjuvant chemotherapy do not exist, and there are no data to support perioperative therapy in cisplatin-ineligible patients. Utilization of neoadjuvant cisplatin is low, attributable in part to patient/physician choice and the advanced age of patients, who often have multiple comorbidities including renal and/or cardiac dysfunction. Trials are using the neoadjuvant paradigm to detect incremental pathologic response to chemobiologic regimens and brief neoadjuvant single-agent therapy to screen for the biologic activity of agents.	bladder
Sunitinib malate provides activity against murine bladder tumor growth and invasion in a preclinical orthotopic model.	OBJECTIVE: To evaluate the effects of sunitinib on localized bladder cancer in a mouse orthotopic bladder tumor model. METHODS: We used an established orthotopic mouse bladder cancer model in syngeneic C3H/He mice. Treatment doses of 40 mg/kg of sunitinib or placebo sterile saline were administrated daily by oral gavage. Tumor volume, intratumoral perfusion, and in vivo vascular endothelial growth factor receptor-2 expression were measured using a targeted contrast-enhanced micro-ultrasound imaging system. The findings were correlated with the total bladder weight, tumor stage, and survival. The effects of sunitinib malate on angiogenesis and cellular proliferation were measured by immunostaining of CD31 and Ki-67. RESULTS: Significant inhibition of tumor growth was seen after sunitinib treatment compared with the control. The incidence of extravesical extension of the bladder tumor and hydroureter in the sunitinib-treated group (30% and 20%, respectively) was lower than the incidence in the control group (66.7% and 55.6%, respectively). Sunitinib therapy prolonged the survival in mice, with statistical significance (log-rank test, P = .03). On targeted contrast-enhanced micro-ultrasound imaging, in vivo vascular endothelial growth factor receptor-2 expression was reduced in the sunitinib group and correlated with a decrease in microvessel density. CONCLUSION: The results of our study have demonstrated the antitumor effects of sunitinib in the mouse localized bladder cancer model. Sunitinib inhibited the growth of bladder tumors and prolonged survival. Given that almost 30% of cases in our treatment arm developed extravesical disease, sunitinib might be suited as a part of a multimodal treatment regimen for bladder cancer.	bladder
Solitary giant sarcomatoid carcinoma of the bladder. A case report.	A case of sarcomatoid carcinoma of the bladder (SCB) presenting as a giant intravesical mass in a 75-year-old man complaining of lower urinary tract swmptoms (LUTS), abdominal pain and fever is reported. SCB is a rare (0.1% of all primary bladder tumors), aggressive cancer with a complex histology (a biphasic tumor with malignant epithelial and mesenchymal elements) and poor prognosis.	bladder
A comparison between blind and nerve stimulation guided obturator nerve block in transurethral resection of bladder tumor.	PURPOSE: To compare blind and nerve stimulation guided transurethral obturator nerve block (ONB) in transurethral resection of bladder tumor (TURBT) to prevent obturator reflex. PATIENTS AND METHODS: One hundred and twelve patients with lateral bladder wall tumors and at high risk for general anesthesia were categorized randomly in three groups. In the first group (34 patients), after spinal analgesia was administered, the exact site of the obturator nerve was determined by nerve stimulation and 15 mL of lidocaine HCl 2% was injected around the nerve. In the second group (31 patients), we determined the obturator nerve using nerve stimulation (like the first group), then 20 mL of saline was injected. In the third group (47 patients), the obturator nerve was determined based on anatomic landmarks and blocked subsequently. Leg jerking was reported and compared in the three groups. RESULTS: The median ages in the three groups were 55.4, 59.4, 57.8 years in the first, second, and third groups, respectively. Male/female ratios were 79.5% in the first, 80.7% in the second, and 80.9% in the third group (P=0.986). Leg jerking was reported in 5.8%, 34%, and 6.3% of patients in the first, second, and third groups, respectively (P=0.0001). ONB took 6.7 minutes in the first, 6.1 minutes in the second, and 5.2 minutes in the third group, on average. There was no report of adverse effects of lidocaine HCl in this study. CONCLUSION: Transvesical ONB is a safe and effective method of ONB before TURBT. This method is feasible by urologists and promising even without nerve stimulation and only by anatomic landmarks.	bladder
The use of pioglitazone and the risk of bladder cancer in people with type 2 diabetes: nested case-control study.	OBJECTIVE: To determine if the use of pioglitazone is associated with an increased risk of incident bladder cancer in people with type 2 diabetes. DESIGN: Retrospective cohort study using a nested case-control analysis. SETTING: Over 600 general practices in the United Kingdom contributing to the general practice research database. PARTICIPANTS: The cohort consisted of people with type 2 diabetes who were newly treated with oral hypoglycaemic agents between 1 January 1988 and 31 December 2009. All incident cases of bladder cancer occurring during follow-up were identified and matched to up to 20 controls on year of birth, year of cohort entry, sex, and duration of follow-up. Exposure was defined as ever use of pioglitazone, along with measures of duration and cumulative dosage. MAIN OUTCOME MEASURE: Risk of incident bladder cancer associated with use of pioglitazone. RESULTS: The cohort included 115,727 new users of oral hypoglycaemic agents, with 470 patients diagnosed as having bladder cancer during follow-up (rate 89.4 per 100,000 person years). The 376 cases of bladder cancer that were diagnosed beyond one year of follow-up were matched to 6699 controls. Overall, ever use of pioglitazone was associated with an increased rate of bladder cancer (rate ratio 1.83, 95% confidence interval 1.10 to 3.05). The rate increased as a function of duration of use, with the highest rate observed in patients exposed for more than 24 months (1.99, 1.14 to 3.45) and in those with a cumulative dosage greater than 28,000 mg (2.54, 1.05 to 6.14). CONCLUSION: The use of pioglitazone is associated with an increased risk of incident bladder cancer among people with type 2 diabetes.	bladder
Long-term survival and onset of granulomatous pneumonia after lung metastasectomy in a patient with non-muscle-invasive bladder cancer.	AIMS: This case report describes a first case of granulomatous pneumonia occurring at the same site of the previous lung metastasectomy in a patient with high-grade non-muscle-invasive bladder cancer (NMIBC), which was treated with bladder preservation therapy despite multiple recurrences and failure of intravesical bacillus Calmette-Guẻrin (BCG) therapy. CLINICAL CASE: We report a 52-year-old woman who underwent transurethral surgery and BCG therapy for pT1, G3 bladder cancer. Although cystectomy was recommended after BCG failure, the operation was not performed because of the patient's wish for bladder preservation. Eighteen months after the first surgery, computed tomography (CT) revealed solitary lung mass. Partial lobectomy which the patient underwent after chemotherapy revealed G3 metastatic urothelial carcinoma. Three years after lung metastasectomy, CT revealed lung mass at the same site of the previous lung metastasectomy. Dynamic contrast-enhanced magnetic resonance imaging showed the significantly enhanced lung mass, which indicated lung metastasis. However, lobectomy of the remnant lobe revealed that the lung mass was granulomatous pneumonia. Although no additional specific treatment was carried out, the patient remains free of disease for 53 months after surgery. CONCLUSIONS: Lung metastasis from NMIBC rarely occurs. Our case report confirms that lung metastasectomy in highly selected patients may contribute to long-term disease control. Moreover, our case report suggests that mycobacterial lung infections along the staple-suture line rarely occur, and percutaneous biopsy should be considered under these circumstances to avoid the unnecessary operation.	bladder
Sulforaphane retards the growth of UM-UC-3 xenographs, induces apoptosis, and reduces survivin in athymic mice.	Sulforaphane (SFN), an isothiocyanate that exists exclusively in cruciferous vegetables, may be the most promising preventive agent for bladder cancer (BC) to date. We previously observed that SFN dramatically inhibits human BC T24 cells in vitro. Our hypothesis is that SFN may attenuate BC growth. To test our hypothesis, we investigated the effect of SFN on human BC UM-UC-3 cell xenografts implanted into athymic mice. Sulforaphane extract was routinely prepared in our laboratory, and its content was measured with high-performance liquid chromatography. Athymic mice were injected subcutaneously with a UM-UC-3 cell suspension (2.0×10(6) cells/200 μL per mouse) and randomly divided into 2 groups. The positive control group was orally gavaged with water, and the treatment group was orally administered SFN from broccoli sprout (12 mg/kg body weight) for 5 weeks. At the end of the experiment, tumor tissues were harvested and processed for hematoxylin and eosin staining and immunohistochemistry. The average tumor volume decreased from 4.1±1.67 cm(3) in the positive control mice to 1.5±0.72 cm(3) in the SFN-treated mice, evidencing an inhibitory rate of 63%. The SFN extract also reduced the appearance of tumors, including karyopyknosis and angiogenesis. Sulforaphane extract induced caspase 3 and cytochrome c expression but reduced the expression of survivin. Sulforaphane extract retards the growth of UM-UC-3 xenografts in vivo, confirming its future potential in BC therapy.	bladder
Validation study of urinary metabolites as potential biomarkers for prostate cancer detection.	BACKGROUND: Urinary metabolomic profiles have recently drawn a lot of attention owing to a debate regarding their possible role as potential clinical markers for prostate cancer. In this study, levels of proline, kynurenine, uracil and glycerol-3-phosphate in 126 patients with genitourinary malignancies were analyzed using a validated method and compared with no evidence of malignancy. RESULTS: The statistical results showed that these biomarkers cannot differentiate prostate cancer from no evidence of malignancy or from other related cancer types, such as bladder cancer. In addition, there was no significant difference in biomarker levels for T1 stages, T2 stages and Gleason scores <7, ≥7. From the correlation study, results showed/demonstrated that age or serum prostate-specific antigen levels do not influence these metabolite concentrations in urine. However, the strong correlation between these metabolites and urinary creatinine concentrations implies that their occurrence is mainly due to renal excretion. CONCLUSION: This detailed study shows that the aforementioned urinary metabolites are not reliable biomarkers for prostate cancer detection or for differentiating the aggressiveness of prostate cancer.	bladder
An evaluation of urinary microRNA reveals a high sensitivity for bladder cancer.	BACKGROUND: Urinary biomarkers are needed to improve the care and reduce the cost of managing bladder cancer. Current biomarkers struggle to identify both high and low-grade cancers due to differing molecular pathways. Changes in microRNA (miR) expression are seen in urothelial carcinogenesis in a phenotype-specific manner. We hypothesised that urinary miRs reflecting low- and high-grade pathways could detect bladder cancers and overcome differences in genetic events seen within the disease. METHODS: We investigated urinary samples (n=121) from patients with bladder cancer (n=68) and age-matched controls (n=53). Fifteen miRs were quantified using real-time PCR. RESULTS: We found that miR is stable within urinary cells despite adverse handling and detected differential expression of 10 miRs from patients with cancer and controls (miRs-15a/15b/24-1/27b/100/135b/203/212/328/1224, ANOVA P<0.05). Individually, miR-1224-3p had the best individual performance with specificity, positive and negative predictive values and concordance of 83%, 83%, 75% and 77%, respectively. The combination of miRs-135b/15b/1224-3p detected bladder cancer with a high sensitivity (94.1%), sufficient specificity (51%) and was correct in 86% of patients (concordance). CONCLUSION: The use of this panel in patients with haematuria would have found 94% of urothelial cell carcinoma, while reducing cystoscopy rates by 26%. However, two invasive cancers (3%) would have been missed.	bladder
Metastatic bladder cancer: anything new?	PURPOSE OF REVIEW: Although bladder cancer is considered a chemosensitive disease, the prognosis of patients with metastatic disease is still poor with median survival being approximately 12-14 months in good prognosis patients and with cure in only a minority of patients. The addition of new drugs to the standard cisplatin-based regimens has not improved these figures. The purpose of this review is to highlight the role of chemotherapy and the impact of the new targeted agents in the treatment of metastatic bladder carcinoma. RECENT FINDINGS: A better understanding of the biology of the molecular patterns of urothelial bladder cancer has led to the clinical investigation of several therapeutic targets such as antiangiogenics, anti-EGFR agents, and immunomodulatory agents. To date, these agents have yet to demonstrate an improvement in overall survival. The molecular alterations that drive platinum resistance and the study of the genetic profiles will help to identify the prognostic and predictive biomarkers. SUMMARY: No major advances have been achieved in the recent years in the treatment of urothelial carcinoma of the bladder. Chemotherapy remains the mainstay of treatment of metastatic disease. Several targeted agents are currently under investigation, but no major breakthroughs have been achieved with these drugs. Development of less toxic, more effective agents is crucial and clinical trial participation needs to be emphasized.	bladder
Ureteric duplication is not a contraindication for robot-assisted laparoscopic radical cystoprostatectomy and intracorporeal Studer pouch formation.	OBJECTIVES: Ureteric duplication is a rarely seen malformation of the urinary tract more commonly seen in females. MATERIALS AND METHODS: We report 2 cases of robot-assisted laparoscopic radical cystoprostatectomy (RALRCP) with bilateral extended pelvic lymph node dissection and intracorporeal Studer pouch formation in patients with duplicated right ureters. RESULTS: Two male patients (53 and 68 years old) underwent transurethral resection of a bladder tumor that revealed high-grade muscle invasive transitional cell carcinoma, with no metastases. We performed RALRCP and intracorporeal Studer pouch formation. A duplicated right ureter was observed during the procedures in both patients. Left ureter distal segment was spatulated 2cm long and anastomosed using running 4/0 Vicryl to the right ureter at its bifurcation where it forms a single lumen without spatulation. All 3 ureters were catheterized individually. A Wallace type uretero-ileal anastomosis was performed between the ureters and the proximal part of the Studer pouch chimney. Although ureteric frozen section analysis suggested ureteric carcinoma in situ in patient 1, postoperative pathologic evaluation was normal. Frozen section and final postoperative pathologic evaluations were normal in patient 2. CONCLUSIONS: Duplicated ureters might be underdiagnosed on CT. The presence of a duplicated ureter is not a contraindication to RALRCP and intracorporeal Studer pouch formation. The da Vinci-S surgical robot is very safe for performing this complicated procedure. Frozen section analysis of ureters during radical cystectomy for bladder cancer might not reliably diagnose the pathologic condition and might overestimate the disease in the ureters.	bladder
Cancer peptide vaccine therapy developed from oncoantigens identified through genome-wide expression profile analysis for bladder cancer.	OBJECTIVE: The field of cancer vaccine therapy is currently expected to become the fourth option in the treatment of cancer after surgery, chemotherapy and radiation therapy. We developed a novel cancer peptide vaccine therapy for bladder cancer through a genome-wide expression profile analysis. METHODS: Among a number of oncoproteins that are transactivated in cancer cells, we focused on M phase phosphoprotein 1 and DEP domain containing 1, both of which are cancer-testis antigens playing critical roles in the growth of bladder cancer cells, as candidate molecules for the development of drugs for bladder cancer. In an attempt to identify the peptide epitope from these oncoantigens, we conducted a clinical trial using these peptides for patients with advanced bladder cancer. RESULTS: We identified HLA-A24-restricted peptide epitopes corresponding to parts of M phase phosphoprotein 1 and DEP domain containing 1 proteins, which could induce peptide-specific cytotoxic T lymphocytes. Using these peptides, we found that M phase phosphoprotein 1- and DEP domain containing 1-derived peptide vaccines could be well tolerated without any serious adverse events, and effectively induced peptide-specific cytotoxic T lymphocytes in vivo. CONCLUSIONS: The novel approach adopted in the treatment with peptide vaccines is considered to be a promising therapy for bladder cancer.	bladder